Rise in complications of acute otitis media during and after the COVID-19 pandemic.

PURPOSE: After the lifting of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, clinical observation showed an increase in complications of acute otitis, followed by a rise in the number of mastoidectomies performed. The aim of this study was to record the number of mastoidectomies performed before, during and after the COVID-19 pandemic as an indicator for complications of acute otitis media. METHODS: Data were collected from a tertiary hospital in a university setting, as well as from four major public health insurance companies in Germany. The data of 24,824,763 German citizens during a period from 2014 until 2023 were analyzed. RESULTS: According to the data, during the COVID-19 pandemic, the number of mastoidectomies performed dropped by 54% for children aged 0-6 and by 62% for children aged 7-18. For adults, there were 30% fewer mastoidectomies performed between 2020 and 2022. After the lifting of most NPI's in the season from July 2022 to June 2023, there was a sharp increase in the number of mastoidectomies performed on patients of all ages. CONCLUSIONS: During the COVID-19 pandemic, a decrease in the number of mastoidectomies performed was seen, suggesting a lower incidence of complicated acute otitis, most likely linked to the general decrease of upper airway infections due to NPI's. In contrast, a sharp increase in the incidence of complicated otitis occurred after the hygiene measures were lifted. The current development causes a more frequent performance of mastoidectomies, thus entailing a change in the challenges for everyday clinical practice.

Changes in the N-glycosylation of porcine immune globulin G during postnatal development.

N-glycosylation influences the effectiveness of immune globulin G (IgG) and thus the immunological downstream responses of immune cells. This impact arises from the presence of N-glycans within the Fc region, which not only alters the conformation of IgG but also influences its steric hindrance. Consequently, these modifications affect the interaction between IgG and its binding partners within the immune system. Moreover, this posttranslational modification vary according to the physiological condition of each individual. In this study, we examined the N-glycosylation of IgG in pigs from birth to five months of age. Our analysis identified a total of 48 distinct N-glycan structures. Remarkably, we observed defined changes in the composition of these N-glycans during postnatal development. The presence of agalactosylated and sialylated structures increases in relation to the number of N-glycans terminated by galactose residues during the first months of life. This shift may indicate a transition from passively transferred antibodies from the colostrum of the sow to the active production of endogenous IgG by the pig's own immune system.

Charge Regulation Triggers Condensation of Short Oligopeptides to Polyelectrolytes.

Electrostatic interactions between charged macromolecules are ubiquitous in biological systems, and they are important also in materials design. Attraction between oppositely charged molecules is often interpreted as if the molecules had a fixed charge, which is not affected by their interaction. Less commonly, charge regulation is invoked to interpret such interactions, i.e., a change of the charge state in response to a change of the local environment. Although some theoretical and simulation studies suggest that charge regulation plays an important role in intermolecular interactions, experimental evidence supporting such a view is very scarce. In the current study, we used a model system, composed of a long polyanion interacting with cationic oligolysines, containing up to 8 lysine residues. We showed using both simulations and experiments that while these lysines are only weakly charged in the absence of the polyanion, they charge up and condense on the polycations if the pH is close to the pKa of the lysine side chains. We show that the lysines coexist in two distinct populations within the same solution: (1) practically nonionized and free in solution; (2) highly ionized and condensed on the polyanion. Using this model system, we demonstrate under what conditions charge regulation plays a significant role in the interactions of oppositely charged macromolecules and generalize our findings beyond the specific system used here.

Role of Natural Binding Proteins in Therapy and Diagnostics.

This review systematically investigates the critical role of natural binding proteins (NBPs), encompassing DNA-, RNA-, carbohydrate-, fatty acid-, and chitin-binding proteins, in the realms of oncology and diagnostics. In an era where cancer continues to pose significant challenges to healthcare systems worldwide, the innovative exploration of NBPs offers a promising frontier for advancing both the diagnostic accuracy and therapeutic efficacy of cancer management strategies. This manuscript provides an in-depth examination of the unique mechanisms by which NBPs interact with specific molecular targets, highlighting their potential to revolutionize cancer diagnostics and therapy. Furthermore, it discusses the burgeoning research on aptamers, demonstrating their utility as 'nucleic acid antibodies' for targeted therapy and precision diagnostics. Despite the promising applications of NBPs and aptamers in enhancing early cancer detection and developing personalized treatment protocols, this review identifies a critical knowledge gap: the need for comprehensive studies to understand the diverse functionalities and therapeutic potentials of NBPs across different cancer types and diagnostic scenarios. By bridging this gap, this manuscript underscores the importance of NBPs and aptamers in paving the way for next-generation diagnostics and targeted cancer treatments.

Outcomes from hematopoietic stem cell transplantation following treosulfan-based conditioning: A clinical and pharmacokinetic analysis.

BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.

Spurious Oscillations Caused by Density Functional Approximations: Who is to Blame? Exchange or Correlation?

We analyze the varying susceptibilities of different density functional approximations (DFAs) to present spurious oscillations on the profiles of several vibrational properties. Among other problems, these spurious oscillations cause significant errors in harmonic and anharmonic IR and Raman frequencies and intensities. This work hinges on a judicious strategy to dissect the exchange and correlation components of DFAs and pinpoint the origins of these oscillations. We identify spurious oscillations in derivatives of all energy components with respect to nuclear displacements, including those energy terms that do not involve numerical integrations. These indirect spurious oscillations are attributed to suboptimal electron densities resulting from a self-consistent field procedure using a DFA that exhibits direct spurious oscillations. Direct oscillations stem from inaccurate numerical integration of the exchange and correlation energy density functionals. A thorough analysis of direct spurious oscillations reveals that only a handful of exchange and correlation components are insensitive to spurious oscillations, giving rise to three families of functionals, BH&H, LSDA, and BLYP. Among the functionals in these families, we encounter four widespread DFAs: BLYP, B3LYP, LC-BLYP, and CAM-B3LYP. Certain DFAs like PBE appear less sensitive to spurious oscillations due to compensatory cancellations between their energy components. Additionally, we found non-negligible but small oscillations in PBE and TPSS, which could be safely employed provided a sufficiently large integration grid is used in the calculations. These findings hint at the key components of current approximations to be improved and emphasize the necessity to develop accurate DFAs suitable for studying molecular spectroscopies.

Dramatic change in the properties of magnetite-modified MOF particles depending on the synthesis approach.

Iron-containing metal-organic frameworks are promising Fenton catalysts. However, the absence of additional modifiers has proven difficult due to the low reaction rates and the inability to manipulate the catalysts. We hypothesize that the production of iron oxide NPs in the presence of a metal-organic framework will increase the rate of the Fenton reaction and lead to the production of particles that can be magnetically manipulated without changing the structure of the components. A comprehensive approach lead to a metal organic framework using the example of MIL-88b (Materials of Institute Lavoisier) modified with iron oxides NPs: formulation of iron oxide in the presence of MIL-88b and vice versa. The synthesis of MIL-88b consists of preparing a complexation compound with the respective structure and addition of terephthalic acid. The synthesis of MIL-88b facilitates to control the topology of the resulting material. Both methods for composite formulation lead to the preservation of the structure of iron oxide, however, a more technologically complex approach to obtaining MIL-88b in the presence of Fe3O4 suddenly turned out to be the more efficient for the release of iron ions.

Design and characterization of an electrochemically-modulated membrane chromatography device.

Membrane separations offer a compelling alternative to traditional chromatographic methods by overcoming mass transport limitations. We introduce an additional degree of freedom in modulating membrane chromatography by using metalized membranes in a potential-driven process. Investigating the impact of a gold coating on membrane characteristics, the sputtered gold layer enhances the surface conductivity with stable electrochemical behavior. However, this comes at the expense of reduced permeability, wettability, and static binding capacity (∼ 474 µg g-1 of maleic acid). The designed device displayed a homogenous flow distribution, and the membrane electrodes exhibit predominantly capacitive behavior during potential application. Modulating the electrical potential during the adsorption and desorption phase strongly influenced the binding and elution behavior of anion-exchange membranes. Switching potentials between ±1.0 V vs. Ag/AgCl induces desorption, confirming the process principle. Elution efficiency reaches up to 58 % at -1.0 V vs. Ag/AgCl in the desorption phase without any alteration of the mobile phase. Increasing the potential perturbation ranging from +1.0 V to -1.0 V vs. Ag/AgCl resulted in reduced peak width and improved elution behavior, demonstrating the feasibility of electrochemically-modulated membrane chromatography. The developed process has great potential as a gentle and sustainable separation step in the biotechnological and chemical industry.

[Multidimensional formats of surgical anatomy in otorhinolaryngology student teaching-a comparison of effectivity]. / Multidimensionale Formate chirurgischer Anatomie in der studentischen Ausbildung der HNO-Heilkunde ­ ein Effektivitätsvergleich.

BACKGROUND: Technological change in healthcare and the digital transformation of teaching require innovations in student teaching in medicine. New technologies are needed to enable the delivery and use of diverse teaching and learning formats by educational institutions independent of time and place. The aim of this study is to analyze the effectiveness of different multidimensional formats in student teaching in surgical ENT medical anatomy. MATERIALS AND METHODS: During the summer semester 2022 and winter semester 2022/2023, the digital teaching and learning program was expanded by testing different visualization formats (3D glasses, cardboards, or VR glasses) with students in the context of a highly standardized surgical procedure, namely cochlear implantation. A pre- and post-intervention knowledge assessment was carried out in all groups, followed by an evaluation. RESULTS: Of 183 students, 91 students fully participated in the study. The post-intervention knowledge assessment showed a significant increase in correct answers regardless of visualization format. In a direct comparison, the operating room (OR) group answered correctly significantly more often than the cardboard group (p = 0.0424). The majority of students would like to see 3D teaching as an integral part of the teaching program (87.9%) and more streaming of live surgeries (93.4%). They see the use of the various technologies as a very good addition to conventional surgical teaching (72.5%), as good visualization (89%) increases retention (74.7%) and motivation (81.3%). CONCLUSION: Application and use of new visualization technologies in everyday clinical practice is a promising approach to expanding student training. Mobile, interactive, and personalized technical formats can be adapted to the learning behavior of students. Last but not least, the use of new media influences learning motivation. An expansion of digital teaching and learning formats can be expressly recommended on the basis of this study.

[Interactive electronic visualization formats in student teaching]. / Interaktive elektronische Visualisierungsformate in der studentischen Ausbildung.

BACKGROUND: In the context of contact restrictions, conventional teaching is currently in need of optimization and expansion. The range of digital teaching formats in student training is very heterogeneous and their effectiveness uncertain. This study aims to investigate the extent to which an electronic ward round can be used as an alternative to the conventional ENT attendance practical course, and whether the use of electronic teaching formats has an influence on the quality of teaching. MATERIALS AND METHODS: Instead of regular attendance practicals, bedside teaching took place once a week in real time as a video stream via tablet. A total of 43 students in the seventh semester (winter semester 2020/2021) were included in the prospective study. Evaluation forms were used to examine the subjective didactic value of different visualization formats for the students. Examination results from previous years were used for comparison. RESULTS: The majority of students reported knowledge gain from the electronic rounds (93.02%) and that they were a good alternative to the traditional attendance clerkship (69.77%). The quality of the video and audio transmission as well as the comprehensibility of the case studies presented were consistently rated as good to very good. The students' examination results tended to be slightly worse in the test group compared to the control students of previous years. CONCLUSION: Integration of innovative interactive visualization options into teaching shows promising prospects as a supplement to conventional face-to-face teaching. The results of this study can contribute to the further expansion of digital teaching. Scaling up this model could be considered especially in countries with limited availability of face-to-face teaching.

Role of the small protein Mco6 in the mitochondrial sorting and assembly machinery.

The majority of mitochondrial precursor proteins are imported through the Tom40 ß-barrel channel of the translocase of the outer membrane (TOM). The sorting and assembly machinery (SAM) is essential for ß-barrel membrane protein insertion into the outer membrane and thus required for the assembly of the TOM complex. Here, we demonstrate that the α-helical outer membrane protein Mco6 co-assembles with the mitochondrial distribution and morphology protein Mdm10 as part of the SAM machinery. MCO6 and MDM10 display a negative genetic interaction, and a mco6-mdm10 yeast double mutant displays reduced levels of the TOM complex. Cells lacking Mco6 affect the levels of Mdm10 and show assembly defects of the TOM complex. Thus, this work uncovers a role of the SAMMco6 complex for the biogenesis of the mitochondrial outer membrane.

Transimpedance Matrix Can Be Used to Estimate Electrode Positions Intraoperatively and to Monitor Their Positional Changes Postoperatively in Cochlear Implant Patients.

OBJECTIVE: Accurate positioning of the electrode array during cochlear implant (CI) surgery is crucial for achieving optimal hearing outcomes. Traditionally, postoperative radiological imaging has been used to assess electrode position. Transimpedance matrix (TIM) measurements have also emerged as a promising method for assessing electrode position. This involves utilizing electric field imaging to create an electric distance matrix by analyzing voltage variations among adjacent electrodes. This study aimed to investigate the feasibility of using intraoperative TIM measurements to estimate electrode position and monitor postoperative changes. STUDY DESIGN: Retrospective cohort study. SETTING: University Medical center, tertiary academic referral center. PATIENTS: Patients undergoing CI (CI622) surgery between January 2019 and June 2022. INTERVENTION: CI electrode positions and maximal angular insertion depths (maxAID) were determined using X-ray imaging according to Stenvers' projection. The mean gradient phase (MGP) was extracted from the TIM, and a correlation between the MGP and maxAID was examined. A model was then built to estimate the maxAID using the MGP, and changes in electrode location over time were assessed using this model. MAIN OUTCOME MEASURES: Twenty-four patients were included in this study. A positive correlation between the maxAID and the MGP ( R = 0.7, p = 0.0001) was found. The established model was able to predict the maxAID with an accuracy of 27.7 ± 4.4°. Comparing intraoperative and postoperative TIM measurements, a decrease of 24.1° ± 10.7° in maxAID over time was observed. CONCLUSION: TIM measurements are useful for estimating the insertion depth of the electrode and monitoring changes in the electrode's position over time.

Parent-Youth Attachment Insecurity and Informant Discrepancies of Intrafamilial Aggression.

This study investigated how youth attachment anxiety and avoidance are associated with informant discrepancies of intrafamilial aggression within families where youth have clinically significant mental health challenges (N = 510 youth-parent dyads). Using polynomial regressions, we tested whether youth attachment avoidance and anxiety moderated the absolute magnitude of the association between youth- and parent-reports of aggression toward each other. Furthermore, difference scores were computed to test whether youth attachment was associated with the direction of youths' reports of the frequency of aggression relative to parents (i.e., did youth under- or over-report). Dyads' reports of youth-to-parent aggression were more strongly related at high than low levels of attachment anxiety. Results also revealed that youth attachment anxiety was associated with youth over-reporting of youth-to-parent and parent-to-youth aggression (relative to parents), whereas attachment avoidance was associated with youth over-reporting parent-to-youth aggression (relative to parents). These findings highlight the importance of understanding the source of informant discrepancies in social-emotional development and family functioning.

Dormancy heterogeneity among Arabidopsis thaliana seeds is linked to individual seed size.

Production of morphologically and physiologically variable seeds is an important strategy that helps plants to survive in unpredictable natural conditions. However, the model plant Arabidopsis thaliana and most agronomically essential crops produce visually homogenous seeds. Using automated phenotype analysis, we observed that small seeds in Arabidopsis tend to have higher primary and secondary dormancy levels than large seeds. Transcriptomic analysis revealed distinct gene expression profiles between large and small seeds. Large seeds have higher expression of translation-related genes implicated in germination competence. By contrast, small seeds have elevated expression of many positive regulators of dormancy, including a key regulator of this process, the DOG1 gene. Differences in DOG1 expression are associated with differential production of its alternative cleavage and polyadenylation isoforms; in small seeds, the proximal poly(A) site is selected, resulting in a short mRNA isoform. Furthermore, single-seed RNA sequencing analysis demonstrated that large seeds resemble DOG1 knockout mutant seeds. Finally, on the single-seed level, expression of genes affected by seed size is correlated with expression of genes that position seeds on the path toward germination. Our results demonstrate an unexpected link between seed size and dormancy phenotypes in a species that produces highly homogenous seed pools, suggesting that the correlation between seed morphology and physiology is more widespread than initially assumed.

Management of Severe Burn Wounds Colonized With Multi-resistant Pseudomonas aeruginosa and Fusarium Using Marine Omega3 Wound Matrix in a Female Victim of War.

War-related burns are common injuries, also among the civilian population. Additional trauma such as fractures or shrapnel wounds may add significant morbidity. Burn injuries in war zones are furthermore frequently undertreated and hence prone to complications. We report a case of a young female victim of war, whose severely infected burn wounds could be successfully healed using a combination of targeted antimicrobial therapy, wound conditioning using decellularized fish skin, and subsequent skin grafting.

Persistent colonization of Candida auris among inpatients rescreened as part of a weekly surveillance program.

We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests.

Head and Neck Cancer: A Study on the Complex Relationship between QoL and Swallowing Function.

Head and neck squamous cell carcinoma (HNSCC) is linked to significant morbidity, adversely affecting survival and functional capacity. Post-treatment challenges such as pain, dysphonia, and dysphagia are common, prompting increased attention in survivorship research. Quality of Life (QoL) questionnaires, especially the MD Anderson Dysphagia Inventory (MDADI), are prevalent outcome measures in clinical studies but often lack parallel objective swallowing function evaluations, leading to potential outcome discrepancies. This study aimed to illuminate the relationship between subjective QoL (EQ-5D-5L and MDADI) measures and objective swallowing function (evaluated via Fiberoptic Endoscopic Evaluation of Swallowing, FEES) in patients with HNSCC. The analysis revealed a notable discordance between objective measures of swallowing function, such as the Penetration-Aspiration Scale (PAS) and residue ratings in the vallecula or piriform sinus, and patients' subjective QoL assessments (p = 0.21). Despite the lack of correlation, swallowing-related QoL, as measured by the MDADI, was more indicative of disease severity than generic QoL assessments. Generic QoL scores did not demonstrate substantial variation between patients. In contrast, MDADI scores significantly declined with advancing tumor stage, multimodal therapy, and reliance on feeding tubes. However, the clinical significance of this finding was tempered by the less than 10-point difference in MDADI scores. The findings of this study underline the limitations of QoL measures as standalone assessments in patients with HNSCC, given their reliance on patient-perceived impairment. While subjective QoL is a crucial aspect of evaluating therapeutic success and patient-centric outcomes, it may fail to capture critical clinical details such as silent aspirations. Consequently, QoL assessments should be augmented by objective evaluations of swallowing function in clinical research and practice to ensure a holistic understanding of patient well-being and treatment impact.

Cancer-specific glycosylation of CD13 impacts its detection and activity in preclinical cancer tissues.

Harnessing the differences between cancer and non-cancer tissues presents new opportunities for selective targeting by anti-cancer drugs. CD13, a heavily glycosylated protein, is one example with significant unmet clinical potential in cancer drug discovery. Despite its high expression and activity in cancers, CD13 is also expressed in many normal tissues. Here, we report differential tissue glycosylation of CD13 across tissues and demonstrate for the first time that the nature and pattern of glycosylation of CD13 in preclinical cancer tissues are distinct compared to normal tissues. We identify cancer-specific O-glycosylation of CD13, which selectively blocks its detection in cancer models but not in normal tissues. In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy.

Tailoring the Preformed Solid Electrolyte Interphase in Lithium Metal Batteries: Impact of Fluoroethylene Carbonate.

The film-forming electrolyte additive/co-solvent fluoroethylene carbonate (FEC) can play a crucial role in enabling high-energy-density lithium metal batteries (LMBs). Its beneficial impact on homogeneous and compact lithium (Li) deposition morphology leads to improved Coulombic efficiency (CE) of the resulting cell chemistry during galvanostatic cycling and consequently an extended cell lifetime. Herein, the impact of this promising additive/co-solvent on selected properties of LMBs is systematically investigated by utilizing an in-house developed lithium pretreatment method. The results reveal that as long as FEC is present in the organic carbonate-based electrolyte, a dense mosaic-like lithium morphology of Li deposits with a reduced polarization of only 20 mV combined with a prolonged cycle life is achieved. When the pretreated Li electrodes with an FEC-derived preformed SEI (pSEI) are galvanostatically cycled with the FEC-free electrolyte, the described benefits induced by the additive are not observable. These results underline that the favorable properties of the FEC-derived SEI are beneficial only if there is unreacted FEC in the electrolyte formulation left to constantly reform the interphase layer, which is especially important for anodes with high-volume changes and dynamic surfaces like lithium metal and lithiated silicon.